FROM SCIENCE TRANSLATIONAL MEDICINE
A newer technique aimed at detect circulating tumor DNA in the blood – cancer personalized profiling by deep sequencing (CAPP-Seq) – detected recurrence of diffuse large B cell lymphoma more than 6 months earlier than radiographic findings in a study at Stanford (Calif.) University, where the technique was invented.
The findings signal another win for “liquid biopsy,” the measurement of tumor DNA circulating in the blood, which is rapidly emerging as a quick and powerful tool for the diagnosis of a range of cancers and tumor subtypes, and prediction of tumor behavior and treatment response. Investigators at Stanford and elsewhere are studying liquid biopsy not only for lymphoma, but also for colorectal, thyroid, breast, prostate, and most other cancers. The Stanford team recently reported that its circulating DNA-detecting CAPP-Seq technique also helps in lung cancer.
In the new study, Stanford used CAPP-Seq (Cancer Personalized Profiling by deep Sequencing), which it called “an ultrasensitive capture-based targeted sequencing method” to analyze 166 plasma and 118 tissue samples from 92 patients with diffuse large B cell lymphoma (DLBCL) at diagnosis and various point afterward. The team compared the results to radiologic, and other standard diagnostic and monitoring techniques ( Sci Transl Med. 2016 Nov 9;8[364]:364ra155 ).
At diagnosis, the amount of circulating DNA (ctDNA) correlated strongly with clinical indices and was independently predictive of patient outcomes; “whereas 100% of pretreatment samples had detectable ctDNA, only 37% of samples had abnormally high serum” lactate dehydrogenase, currently the most commonly used biomarker for DLBCL, said investigators, led by research fellow Florian Scherer, MD.
The group detected ctDNA in 73% of patients (8/11) who eventually relapsed a mean of 188 days before relapse was detected by standard-of-care radiologic techniques.
CAPP-Seq identified nine patients with a particular type of activated B cell-like tumor, for whom ibrutinib (Imbruvica) is particularly effective; ctDNA also predicted the transformation of indolent follicular lymphoma to DLBCL “with high sensitivity and specificity,” the group reported.
Stanford anticipates “ctDNA will have broad utility for dissecting tumor heterogeneity within and between patients with lymphomas and other cancer types, with applications for the identification of adverse risk groups, the discovery of resistance mechanisms to diverse therapies, and the development of risk-adapted therapeutics.”
The team said its approach “outperformed immunoglobulin sequencing and radiographic imaging for the detection of minimal residual disease and facilitated noninvasive identification of emergent resistance mutations to targeted therapies.” Meanwhile, while biomarkers hold “great promise for risk stratification and therapeutic targeting,” they are “currently difficult to measure in clinical settings,” the investigators said.
Roche bought the rights to CAPP-Seq from Stanford in 2015. Several authors are coinventors on patent applications for CAPP-Seq and also Roche consultants. Two are employees. Dr. Scherer had no disclosures. The work was funded by Stanford, the American Society of Hematology, the National Cancer Institute, and others.
